Synthesis and evaluation of L-arabinose-based cationic glycolipids as effective vectors for pDNA and siRNA in vitro

Abstract

Glycolipids might become a new type of promising non-viral gene delivery systems because of their low cytotoxicity, structural diversity, controllable aqua- and lipo-solubility, appropriate density and distribution of positive charges, high transfer efficiency and potential targeting function. In this study, four kinds of L-arabinose-based cationic glycolipids (Ara-DiC12MA, Ara-DiC14MA, Ara-DiC16MA and Ara-DiC18MA) containing quaternary ammonium as hydrophilic headgroup and two alkane chains as hydrophobic domain were synthesized and characterized. They were observed to have strong affinities for plasmid DNA (pDNA) and siRNA, the pDNA can be completely condensed at N/P ratio less than 2, and the siRNA can be completely retarded at N/P ratio less than 3. The dynamic light scattering (DLS) experiment and atomic force microscopy (AFM) experiment demonstrated that cationic lipids and their lipoplexes possessed suitable particle sizes with near-spherical shape and proper ζ-potentials for cell transfection. The Ara-DiC16MA liposome was found to have good transfection efficacy in HEK293, PC-3 and Mat cells compared with other three kinds of liposomes, and also maintain low cytotoxicity and better uptake capability in vitro. Furthermore, the gene silencing assay showed that Ara-DiC14MA and Ara-DiC16MA liposomes have demonstrated effective delivery and higher gene knockdown activity (>80%) in the above mentioned cells than Lipofectamine 2000. These results indicated Ara-DiC16MA can be developed for efficient and low toxic gene delivery.

Efficient Modulation of β-Amyloid Peptide Fibrillation with Polymer Nanoparticles Revealed by Super-Resolution Optical Microscopy

“…Poly [(9,9-dioctylfluorenyl-2,7-diyl)- alt - co -(1,4-benzo-(2,1′,3)-thiadiazole)] (PFBT) was purchased from American Dye Source, Inc. (Quebec, Canada). Propylene glycol amine cationic lipids were gifted from Prof. Dr. Youlin Zeng (Hunan Normal University, China, Chinese patent: #201110444269.5) . The chemical structure of propylene glycol amine cationic lipid is shown in Figure a.…”

“…More interestingly, according to the timedependent single-particle fluorescence characterizations, the small-sized CPNPs show a character of burst-like blinking behavior, analogous to Qdots, which is well suited for localization-based super-resolution imaging. 32,39 By sequentially recording the particle position, a spatial resolution of 20 nm was readily achieved, which was further applied for the 40 The chemical structure of propylene glycol amine cationic lipid is shown in Figure 1a. β-Amyloid (1−40) was purchased from AnaSpec, Inc. (Fremont, U.S.A.).…”

Lipophilic Polyamines as Promising Components of Liposomal Gene Delivery Systems

“…The CA structure significantly affects the efficiency of NA delivery to eukaryotic cells. In recent years, many monocationic amphiphiles have been obtained [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] that form liposomes for NA delivery. In this review, we will consider polycationic amphiphiles, which, compared to monocationic analogs, enable the more efficient transport of NAs into cells due to the formation of a system of distributed charges in the polyamine matrix and their ability to facilitate NA release from endosomes.…”